title: A novel investigational Fc-modified humanized monoclonal antibody, motavizumab-YTE, has an extended half-life in healthy adults.
abstract: The study objective was to evaluate the pharmacokinetics (PK), antidrug antibody (ADA), and safety of motavizumab-YTE (motavizumab with amino acid substitutions M252Y/S254T/T256E [YTE]), an Fc-modified anti-respiratory syncytial virus (RSV) monoclonal antibody. Healthy adults (n = 31) were randomized to receive a single intravenous (i.v.) dose of motavizumab-YTE or motavizumab (0.3, 3, 15, or 30 mg/kg) and followed for 240 days. Clearance of motavizumab-YTE was significantly lower (71% to 86%) and the half-life (t1/2) was 2- to 4-fold longer than with motavizumab. However, similar peak concentrations and volume-of-distribution values, indicative of similar distribution properties, were seen at all dose levels. The sustained serum concentrations of motavizumab-YTE were fully functional, as shown by RSV neutralizing activity that persisted for 240 days with motavizumab-YTE versus 90 days postdose for motavizumab. Safety and incidence of ADA were comparable between groups. In this first study of an Fc-modified monoclonal antibody in humans, motavizumab-YTE was well tolerated and exhibited an extended half-life of up to 100 days. (This study has been registered at ClinicalTrials.gov under registration no. NCT00578682.).
authors.affiliation: Clinical Pharmacology and DMPK.
authors.forename: Gabriel J
authors.initials: GJ
authors.lastname: Robbie
authors.forename: Ryan
authors.initials: R
authors.lastname: Criste
authors.forename: William F
authors.initials: WF
authors.lastname: Dall'acqua
authors.forename: Kathryn
authors.initials: K
authors.lastname: Jensen
authors.forename: Nita K
authors.initials: NK
authors.lastname: Patel
authors.forename: Genevieve A
authors.initials: GA
authors.lastname: Losonsky
authors.forename: M Pamela
authors.initials: MP
authors.lastname: Griffin
mesh_terms: D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000097:blood / Q000493:pharmacokinetics*; D000998:Antiviral Agents / Q000097:blood / Q000493:pharmacokinetics*; D004311:Double-Blind Method; D015507:Drugs, Investigational / Q000493:pharmacokinetics*; D005260:Female; D006207:Half-Life; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000737:chemistry*; D007275:Injections, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000998:Antiviral Agents; D015507:Drugs, Investigational; D007141:Immunoglobulin Fc Fragments; C506968:motavizumab